DESCRIPTION: (Principal Investigator's) This project will continue the development of a fundamentally new methodology for the activation and functionalization of aromatic heterocycles. The cornerstone of this approach i to selectively and reversibly dearomatize the heterocycle (e.g. pyrrole or furan) through eta2-complexation to a transition metal, and to use this adduct as a synthon for the assembly of functionalized carbocycles and heterocycles. Coordination of the aromatic heterocycle serves 1) to enhance the reactivity o the heterocycle towards electrophiles, 2) to stabilize reactive intermediates (e.g. pyrrolium, furanium, allyl, and vinyl cations) thereby facilitating assembly of various polycyclic structures, 3) to direct the stereochemistry of these chemical transformations, and 4) to protect the site of coordination for additional transformations. Once developed, this technology could have a dramatic impact on the ability of synthetic chemists to rapidly and efficientl produce milligram to gram quantities of potentially pharmacologically valuable compounds starting from widely available aromatic precursors, which in turn would facilitate the execution of structure/activity relationship studies required for optimization of new pharmaceuticals. In a number of cases within the main body of the proposal, transformations are described for which there i presently no conventional organic or organometallic synthetic method available The immediate goal of this research is to demonstrate the potential and versatility of transition-metal based eta2-complexing agents in organic synthesis. To best accomplish this, elementary transformations have been chose for study in the context of their comparison to contemporary synthetic methods and these will be accomplished using a proven osmium-based complexing agent. This program will also address the design of alternative transition metal complexes which could match or improve on the performance of the existing pentaammineosmium(II) system.